DESCRIPTION (provided by principal investigator): Our application is in response to NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. The parent grant is 5U01AG017155-08, Epidemiology of Aging and Dementia-Autopsy Research. We will address three distinct neuropathologic abnormalities found in the brains of substantial proportions of demented HAAS decedents, but that were not recognized as important causes of cognitive deterioration when the parent grant was originally designed. They are: 1) dementia lacking distinctive histopathology, 2) hippocampal sclerosis, and 3) microinfarcts. All relevant brain materials are available "wet" (in neutral formalin) or paraffin embedded. Subset panels for each of these three lesion types have been selected to minimize ambiguity related to co-morbid lesions, and for the examination of relevant comparison groups. Intensive state-of-the-art histologic methods will be applied to these panels to define their possible relationships with other known conditions (fronto-temporal dementia, motor neuron disease, chronic ischemia or chronic inflammatory states) as well as to examine possible inter-relatedness and occurrence in non-impaired decedents. Research on microinfarcts will greatly extend our understanding of optimal methods for their detection, of their distribution throughout the brain in relation to cognitive impairment, and will provide a basis for pathologic criteria for the diagnosis of "multi-microinfarct dementia" as a major category of vascular cognitive impairment. Research bearing on MRI approaches to the diagnosis of multi-microinfarct dementia during life will be carried out using brain tissues selected to be maximally informative for these purposes. The results of these efforts will have a major impact on current concepts related to the causes of dementia in late life, and will be highly relevant to the development of preventive strategies to reduce the human and public health burden of these terrible afflictions. Major economic benefits are related to the support of new employees, increasing the level of effort of part time employees, and the purchase of essential laboratory equipment and materials needed to carry out the proposed work. PUBLIC HEALTH RELEVANCE: The results of our research will have a major impact on current concepts related to the causes of dementia in late life, and will be highly relevant to the development of preventive strategies to reduce the human and public health burden of these terrible afflictions.